Determining the magnitude of the burden of diseases and health disorders on the U.S. population is a high priority for health policy makers. Conditions such as malignant neoplasms and injuries from craniofacial trauma contribute to adverse oral health. This study estimates the number of cases of diseases and disorders relevant to oral health that are treated annually in the medical care, as opposed to the dental care, system and associated costs. Policy makers can use this cost model to compare the impact of different conditions, to target areas for reducing costs, and to allocate appropriate health resources. Data from four national and two state data systems were used to estimate the number of cases of selected dental, oral, and craniofacial diseases and conditions treated in the medical system annually and associated medical and wage/household work loss costs. Per case, the most costly conditions were estimated to be malignant neoplasms at 83,080 US dollars annually (in 1999 dollars), diabetes-related oral conditions at 51,030 US dollars, endocarditis at 48,610 US dollars, and chlamydiae at 41,100 US dollars. Total estimated costs for oral conditions treated in the medical care system in 1996 were approximately 95.9 billion US dollars, including 21.4 billion US dollars in medical costs and 74.4 US dollars billion in wage/household work loss costs. Conditions treated outside the dental care system are major contributors to oral health costs. They should be an important focus for the National Institute of Dental and Craniofacial Research.